Genetic changes in blood predict AML risk

17 July 2018

It could be possible to identify people most at risk of developing acute myeloid leukaemia (AML) several years before they receive a diagnosis, according to a new European study.

An international study, involving the Wellcome Sanger Institute, UK, and the European Bioinformatics Institute (EMBL-EBI), has found that patients with AML experienced genetic changes in their blood years before they developed the disease.

The study, published in Nature, found that changes in the DNA code can reveal the roots of AML in healthy people and that further research could allow earlier detection and monitoring of people at risk of AML.

The research team, which also included scientists from the Princess Margaret Cancer Centre in Canada and the Weizmann Institute in Israel, collaborated with the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a health and lifestyle study that tracked 550,000 people over 20 years to determine correlations to cancer.

They sequenced the DNA from blood collected from 124 AML patients and compared it to 676 people who did not develop AML or a related cancer.

The study focused on selected genes known to be associated with AML, and found frequent mutations in some of these genes in many individuals, including those who did not develop AML.

However, people who went on to develop the disease were found to have a higher number of mutations and the mutations were often present in a larger fraction of their blood cells. Specific blood test results were also found to be subtly different in those who later developed AML.

Co-principal investigator Dr John Dick, senior scientist at Princess Margaret Cancer Centre, University Health Network, described the findings as the ‘black box of leukaemia’.

"We have been able to identify people in the general population who have traces of mutations in their blood that represent the first steps in how normal blood cells begin on a pathway of becoming increasingly abnormal and puts them at risk of progressing to AML,” he said.

“We can find these traces up to 10 years before AML actually develops. This long time window gives us the first opportunity to think about how to prevent AML."

Dr Grace Collord, joint first author on the paper from the Wellcome Sanger Institute and University of Cambridge, said: “Acute myeloid leukaemia often appears very suddenly in patients, so we were surprised to discover that its origins are generally detectable more than five years before the disease develops. This provides proof-of-principle that it may be possible to develop tests to identify people at a high risk of developing AML.”

With about five in 100,000 people in the general population developing AML each year, predictive tests would have to be highly accurate to minimise the risk of false positive results, which means further studies must be undertaken to enhance the accuracy of predictive tests to make them robust enough to use clinically, say the authors.

Dr George Vassiliou, one of the joint leaders of the project from the Wellcome Sanger Institute and the Wellcome-MRC Cambridge Stem Cell Institute, and consultant haematologist at Cambridge University Hospitals NHS Trust, said: “Our study provides, for the first-time, evidence that we can identify people at risk of developing AML many years before they actually develop this life-threatening disease.

“We hope to build on these findings to develop robust screening tests for identifying those at risk and drive research into how to prevent or stall progression towards AML. Our aspiration is that one day AML prevention would provide a compelling alternative to treatment.”

Disclaimer: The news stories shared on this site are used as a way to inform our members and followers of updates and relevant information happening in Haematology. The BSH does not endorse the content of news items from external sources, and is not in a position to verify the findings, accuracy or the source of any studies mentioned. Any medical or drugs information is provided as an information resource only, and is not to be relied on for any diagnostic or treatment purposes.

The British Society for Haematology is registered in England and Wales as a Company Limited by Guarantee, No 2645706 and as a Charity, No 1005735 Registered Office and correspondence address: 100 White Lion Street London N1 9PF. Phone: 020 7713 0990
Temporary Office (October 2018 until further notice): British Society for Haematology, c/o Suite 3.11/3.12, Evergreen House North, Grafton Place, London, NW1 2DX